The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome.

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment. METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores. RESULTS: Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively). CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.

Thyroid function in early and late alcohol withdrawal: relationship with aggression, family history, and onset age of alcoholism.

AIMS: Thyroid dysfunction is a known finding in alcoholism. Most studies have reported the reduction in peripheral thyroid hormones in acute withdrawal and long-term abstinence periods of alcohol dependence. The aim of the present study was to investigate the alterations of free thyroid hormones in early and late withdrawal and their association with aggression, age of onset, and family history of alcoholism. METHODS: Male inpatients (n = 39; mean age +/- SD: 42.55 +/- 8.02 years) in alcohol withdrawal were compared with healthy men (n = 28; mean age +/- SD: 38.31 +/- 9.26 years). Levels of free thyroxine (fT4), free triiodothyronine, (fT3) and thyrothrophin (TSH) were measured in early (first day) and late (28th day) withdrawal in the patients and only once in the controls. RESULTS: In early withdrawal, levels of thyroid hormones did not differ from those in the controls. In late withdrawal, fT3 and fT4 levels (2.71 +/- 0.56 and 10.80 +/- 1.86 pg/ml) were lower than those of both controls (3.32 +/- 0.41 and 11.95 +/- 1.49 pg/ml, respectively, P < 0.05 in both cases) and patients in early withdrawal (3.18 +/- 0.72 and 12.68 +/- 2.50 pg/ml, respectively, P < 0.05 in both cases). Patients were divided into subgroups according to aggression level, onset age of alcoholism, and family history. While the high-aggression group had lower serum levels of fT3 and fT4 in late withdrawal (2.49 +/- 0.41 and 10.44 +/- 2.15 pg/ml) compared with those of controls (P < 0.05 in both cases), the low-aggression group only had lower serum levels of fT3 in late withdrawal (2.90 +/- 0.62 pg/ml) compared with those of controls (P < 0.05). fT3 and fT4 values in the family history-negative group (2.67 +/- 0.56 and 10.75 +/- 1.88 pg/ml) were lower than those of controls in late withdrawal (P < 0.05 in both cases). Both fT3 and fT4 levels in late withdrawal (2.69 +/- 0.54 and 10.83 +/- 1.96 pg/ml) were decreased in early-onset group compared with those of controls (P < 0.05 in both cases). CONCLUSION: Decreased free thyroid hormone levels may be a result of heavy alcohol consumption or a trait marker of alcoholism, especially in high-aggressive, early-onset and family history-negative patients.

Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression.

Leptin is a product of the obese gene and plays an important role in the regulation of body weight and food intake. Weight and appetite are frequently altered in depression. So far, inconsistent results have been reported in terms of leptin levels in depression. Therefore, the authors investigated serum leptin levels in patients with depression and in healthy controls, and whether there was any alteration throughout antidepressant treatment. Female patients showed significantly higher leptin levels than those of the control females both before and after the response to antidepressant treatment, whereas no difference was found between the male patients and the male controls. The improvement from depression with antidepressant treatment caused a further elevation on the leptin levels, in both female and male patients. These findings confirm an increase in leptin levels in depressive patients and presence of a sexual dimorphism. Moreover, clinical response to antidepressant treatment seems to have an additional increasing effect on leptin levels.

Effects of electroconvulsive therapy on the thyrotropin-releasing hormone test in patients with depression.

We investigated the acute and lasting effects of electroconvulsive therapy (ECT) on the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in patients with depression. The TRH stimulation test was conducted (1) under basal conditions, after a first ECT, and at the end of a therapeutic course of 7 ECTs in 20 inpatients with depression; (2) before the initiation of antidepressant therapy and after the therapeutic response in 16 other inpatients with depression who responded to antidepressant drug treatment; and (3) in 20 healthy control subjects. Baseline TSH levels were lower in patients with depression, especially in those with more severe depression who were considered appropriate for ECT. Before the treatment, TSH response to TRH did not differ between the patients with depression and controls; however, more blunted TSH responses to TRH were observed in these patients compared with the controls. TSH response to TRH changed neither with one ECT nor throughout consecutive ECT sessions in patients with depression. Drug treatment also was found to have no impact on this response. These findings suggest that the therapeutic action of ECT in depression is not directly related to its effects on the hypothalamic-pituitary-thyroid axis. However, possible delayed effects of ECT on the HPT axis function should not be overlooked.

Effects of antidepressant treatment on thyrotropin-releasing hormone stimulation, growth hormone response to L-DOPA, and dexamethasone suppression tests in major depressive patients.

Dexamethasone suppression (DST), thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) and growth hormone (GH) response to L-DOPA tests were evaluated in 19 depressed inpatients before the commencement of the antidepressant treatment and after the clinical response to examine: (i) the functional relationships among the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis and dopaminergic system in depression, (ii) any alterations in these hormonal functions with the antidepressant treatment. TSH responses to TRH showed a tendency to increase from pre- to posttreatment period, while TRH-induced PRL and L-DOPA-induced GH responses did not change with treatment in depressed patients who responded to the treatment. Females showed significantly higher TSH and PRL responses to TRH compared to males. No interconnections were found among the responses in DST, TRH stimulation test and L-DOPA-induced GH test in the patients. The results do not support the interrelations between the abnormalities in the HPT and HPA axes and central dopaminergic activity in depression.

A Tc-99m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome.

Twenty-nine patients with DSM-IV diagnoses of schizophrenia were categorized into deficit syndrome (n=14) and non-deficit syndrome (n=15) subgroups on the basis of the Schedule for the Deficit Syndrome. The patients, who had all been free of antipsychotic medication for at least 3 weeks, and 17 sex- and age-matched normal controls were studied with single-photon emission computed tomography with Tc-99m HMPAO. Age at onset, Brief Psychiatric Rating Scale (BPRS) total scores, BPRS positive symptom subscores and duration of illness were similar between the two schizophrenic subgroups. As expected, the deficit patients had more negative symptoms than the non-deficit patients. There were no statistically significant correlations between clinical parameters and regional cerebral blood flow (rCBF) values. The deficit syndrome subgroup showed diminished rCBF in the frontal regions bilaterally, right parietal regions and right superior temporal region compared with the control groups. Deficit patients showed significantly lower rCBF perfusion ratios in the right superior and inferior frontal cortex than did the non-deficit patients. No differences were detected between the controls and the non-deficit schizophrenic patients in terms of rCBF perfusion indices. The results of the present study confirm previous reports of different patterns of rCBF in deficit vs. non-deficit schizophrenic subgroups.

Tc-99 HMPAO SPECT study of regional cerebral blood flow in olanzapine-treated schizophrenic patients.

Dopamine D(2) blocking typical antipsychotic drugs are known to change the cerebral perfusion patterns of schizophrenic patients, especially in the frontal cortex and basal ganglia. In recent years atypical antipsychotics such as olanzapine, which have high serotonin 5-HT(2A)/dopamine D(2) occupation ratios, have been shown to be more effective in the treatment of schizophrenia symptoms. The aim of this study was to evaluate the regional cerebral blood flow (rCBF) of the schizophrenic patients treated with olanzapine in a within-subject design. Twenty-four patients with schizophrenia participated as subjects in the study. Each subject was scanned in a medication-free state and after 6 weeks of 10 mg/day fixed dose olanzapine treatment. Despite the clinical improvement seen in the patients, repeated-measures analysis of variance showed that olanzapine produced no significant changes in cortical rCBF after the six-week treatment. This finding indicates that unlike typical antipsychotics olanzapine has no negative effect on cortical cerebral perfusion patterns of schizophrenic patients.

Effects of electroconvulsive therapy on hypothalamic-pituitary-thyroid axis activity in depressed patients.

In this study, the authors aimed to test the hypothesis that electroconvulsive therapy (ECT) may cause some alterations in hypothalamic-pituitary-thyroid (HPT) axis hormones and these responses may change throughout respective ECT sessions. Nineteen depressed inpatients (8 males, 11 females; mean age+/-S.D.: 44.77+/-10.59 years) considered suitable for ECT were included in the study. Each patient was exposed to 7 ECT sessions with general anaesthesia. The blood samples for measurements of thyroid-stimulating hormone (TSH), free thyroiodothyronine (fT3) and free thyroxine (fT4) were drawn before (baseline) and after propofol, immediately after ECT, and 30 and 60 min after ECT during the first and last (seventh) ECTs. In both the first and seventh ECTs, there was a significant increase in TSH levels 30 min after ECT compared to the pre-ECT values. Additionally, a significant decrease in post-ECT fT4 values compared to the baseline values was found only during the seventh ECT. No difference was detected in the TSH, fT3 and fT4 responses to ECT between males and females, and between bipolar and unipolar depressive patients. These results show that ECT may have some effects on the HPT system. However, whether there is a relationship between these neuroendocrine responses and the therapeutic effect of ECT is not clear.

Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder.

Lithium (Li) carbonate has been reported to be able to cause some reversible functional changes in the kidney. In this study, the authors aimed to investigate whether the duration of Li treatment is the primary determinant of the changes in renal functioning due to the Li treatment. For this purpose, 10 Li-naïve (mean age+/-S.D.: 34.50+/-4.85), 10 short-term (mean age+/-S.D.: 31.77+/-7.61) and 10 long-term (mean age+/-S.D.: 36.60+/-10.15) Li-treated bipolar patients were included in the study. Serum blood urea nitrogen (BUN) and creatinine, urine creatinine levels, creatinine clearance, urine osmolality before and after 8-h water deprivation and urine osmolality after desmopressin injection were measured in all patients. Serum BUN and creatinine levels were within the normal limits and not statistically different among the groups. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-naïve group and that of the short-term Li-treated group. After 8-h water deprivation and also after desmopressin injection, no difference was found among the groups in terms of urine osmolality. However, when each patient was evaluated individually in terms of their renal concentrating ability, partial nephrogenic diabetes insipidus was diagnosed in four patients on long-term and in two patients on short-term Li treatment. To our surprise, hypothalamic diabetes insipidus was also diagnosed in other two patients on long-term Li treatment. These results demonstrate that long-term Li treatment may cause impairment in renal concentrating ability, some of which may originate from the effects of Li on vasopressin on hypothalamic level, and a decrease in glomerular filtration rate (GFR). In the light of these data, we can conclude that long-term administration of Li may be a risk factor for Li-induced renal impairment, which is a progressive effect in nature.

Monoamine oxidase-B activity in alcohol withdrawal of smokers: is there any relationship with aggressiveness?

There is a considerable inconsistency in terms of the association between alcoholism and alterations in monoamine oxidase (MAO) activity. The main objectives of this study were to investigate the changes in platelet MAO-B activity throughout the alcohol withdrawal period and whether or not MAO-B activity differed between patients with high- and low-aggression tendency. We assayed platelet MAO-B levels spectrophotometrically in 22 male inpatients with alcohol dependence in their first and fourth weeks of withdrawal and in 20 healthy controls. Patients were divided into two high- and low-aggression subgroups according to scores obtained in a Brown-Goodwin Assessment for Life History of Aggression. Our data revealed that the significantly lower platelet MAO-B activity observed during the first week of alcohol withdrawal in patients, compared to controls, did not continue in the fourth week, and that there was no relationship between aggressiveness and MAO activity. These results suggest that low platelet MAO activity may be a state marker of alcohol withdrawal period or a result of high alcohol consumption rather than a trait marker of alcoholism.